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排序方式: 共有1820条查询结果,搜索用时 15 毫秒
41.
Tanaka T Masuzaki H Ebihara K Ogawa Y Yasue S Yukioka H Chusho H Miyanaga F Miyazawa T Fujimoto M Kusakabe T Kobayashi N Hayashi T Hosoda K Nakao K 《Metabolism: clinical and experimental》2005,54(11):1490-1498
Steatosis is one of the most common liver diseases and is associated with the metabolic syndrome. A line of evidence suggests that peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma are involved in its pathogenesis. Hepatic overexpression of PPARgamma1 in mice provokes steatosis, whereas liver-specific PPARgamma disruption ameliorates steatosis in ob/ob mice, suggesting that hepatic PPARgamma functions as an aggravator of steatosis. In contrast, PPARalpha-null mice are susceptible to steatosis because of reduced hepatic fatty acid oxidation. PPARgamma with mutations in its C-terminal ligand-binding domain (L468A/E471A mutant PPARgamma1) have been reported as a constitutive repressor of both PPARalpha and PPARgamma activities in vitro. To elucidate the effect of co-suppression of PPARalpha and PPARgamma on steatosis, we generated mutant PPARgamma transgenic mice (Liver mt PPARgamma Tg) under the control of liver-specific human serum amyloid P component promoter. In the liver of transgenic mice, PPARalpha and PPARgamma agonist-induced augmentation of the expression of downstream target genes of PPARalpha and PPARgamma, respectively, was significantly attenuated, suggesting PPARalpha and PPARgamma co-suppression in vivo. Suppression of PPARalpha and PPARgamma target genes was also observed in the fasted and high-fat-fed conditions. Liver mt PPARgamma Tg were susceptible to fasting-induced steatosis while being protected against high-fat diet-induced steatosis. The opposite hepatic outcomes in Liver mt PPARgamma Tg as a result of fasting and high-fat feeding may indicate distinct roles of PPARalpha and PPARgamma in 2 different types of nutritionally provoked steatosis. 相似文献
42.
Matsumoto M Zhou Y Matsuo S Nakanishi H Hirose K Oura H Arase S Ishida-Yamamoto A Bando Y Izumi K Kiyonari H Oshima N Nakayama R Matsushima A Hirota F Mouri Y Kuroda N Sano S Chaplin DD 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(18):6720-6724
Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus (PSORS1) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn-deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn-deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility. 相似文献
43.
44.
A giant retention cyst of the pancreas (cystic dilatation of dorsal pancreatic duct) associated with pancreas divisum 总被引:1,自引:0,他引:1
Morise Z Yamafuji K Tsuji T Asami A Takeshima K Hayashi N Baba H Yoshida F Abe Y Tokura Y 《Journal of gastroenterology》2002,37(12):1079-1082
We describe a rare case of pancreas divisum associated with a giant retention cyst (cystic dilatation of the dorsal pancreatic
duct), presumably formed following obstruction of the minor papilla. The patient was treated by pancreatico(cysto)jejunostomy.
A 50-year-old man was admitted with complaints of increasing upper abdominal distension and body weight loss. There was no
previous history of pancreatitis, gallstones, drinking, or abdominal injury. An elastic-hard tumor-like resistance was palpable
in the upper abdomen. Computed tomography and ultrasound (US) examinations revealed a giant cystic lesion expanding from the
pancreas head to the tail. Endoscopic retrograde cholangiopancreatography findings showed a looping pancreatic duct which
drained only the head and uncinate process of the pancreas to the main papilla. A US-guided puncture to the cystic lesion
revealed that the lesion continued to the main pancreatic duct in the tail of pancreas. The lesion was connected to a small
cystic lesion, which was located inside the minor papilla, and ended there. The amylase level in liquid aspirated from the
cyst was 37 869 IU/l, and the result of cytological examination of the liquid showed class II. A pancreatico(cysto)jejunostomy
was performed, with the diagnosis being pancreas divisum associated with a retention cyst following obstruction of the minor
papilla. The histological findings of a specimen from the cyst wall revealed that the wall was a pancreatic duct covered with
mildly inflammatory duct epithelium; there was no evidence of neoplasm. The patient is currently well, and a CT examination
2 years after the operation showed disappearance of the cyst and normal appearance of the whole pancreas.
Received: April 24, 2001 / Accepted: September 14, 2001 相似文献
45.
46.
Takeuchi J Ly H Yamaguchi H Carroll KA Kosaka F Sawaguchi K Mitamura Y Watanabe A Gomi S Inokuchi K Dan K 《Blood cells, molecules & diseases》2008,40(2):185-191
As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia. 相似文献
47.
48.
Nozomu Takeuchi Fumiko Tanaka Yoshiyuki Katayama Kazuto Matsumiya Yuichi Yamamura 《Experimental gerontology》1976,11(5-6)
Thiobarbituric acid reactive substances (TBARS) increased in hepatic microsome fractions from rats aged 3 months as compared with such fractions from 1-month-old rats, though serum TBARS concentration did not differ between groups. Serum TBARS concentrations became significantly higher in adult rats aged 6–7 and 12–13 months than in those month old. TBARS reactions in mitochondria did not show such clear age-related change.Administration of a diet containing 0·5 per cent tocopherol to rats for 1–3 months, lowered the TBARS concentrations in microsomes concomitantly with a decrease of serum TBARS concentrations. In these rats, synthetic activities of cholesterol and fatty acid in the hepatic microsomes from acetate or mevalonate were similar in both treated and non-treated control groups. However, the activity was higher in the treated group than in the non-treated control after long-term (up to 6 months) feeding of tocopherol. Serum cholesterol, phospholipid and triglyceride concentrations in rats treated with tocopherol for 6 months were significantly lower than those in control rats. 相似文献
49.
Keiko Nishizawa Kenta Teruya Ayumi Oguma Yuji Sakasegawa Hermann Schätzl Sabine Gilch Katsumi Doh-ura 《Journal of pharmaceutical sciences》2019,108(8):2814-2820
Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC50 dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prion-infected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action. 相似文献
50.